In this cross-sectional study, we utilized data from Tianjin based on the TIDE-2014 dataset to investigate the impact of iodine malnutrition on AITD. Previous literature reports suggest that the prevalence of AITDs in the population is approximately 5%, and there is a significant gender difference in disease risk, with women being more susceptible than men[16], which aligns with our research findings. Tg, a glycoprotein with a molecular weight of 660,000, has been observed to be significantly elevated in the serum of individuals with thyroid diseases, particularly thyroid cancer [17]. The production of TgAb is a key characteristic of AITDs, while serum TgAb alone is not considered diagnostically conclusive, and the diagnosis of AITDs typically necessitates confirmation through multiple detection indicators [8].
We classified the research population into four groups based on the UIC grouping recommended by the WHO/ICCIDD [15]. Our analysis revealed that the positive rate of TGAb in the DI group and the EI group is significantly higher than that of the AI group and the MAI group. Adverse effects resulting from inadequate or excessive iodine levels may contribute to an increased TgAb positive rate, subsequently influencing the occurrence of AITDs. Some scholars have suggested that long-term excessive iodine intake can induce autoimmune thyroiditis, partly due to the increased immunogenicity of high-iodine Tg [18].
In comparison to the healthy control group, the case group exhibited lower levels of Tg concentration. However, the case group showed significantly higher values for the indicators SI/Tg, snPBI/Tg, and sPBI/Tg compared to the healthy control group. Additionally, the levels of TgAb in the case group were significantly elevated compared to the healthy control group. SI/Tg represents the ratio of serum iodine to Tg, snPBI/Tg represents the ratio of serum non-protein-bound iodine to Tg, and sPBI/Tg represents the ratio of serum protein-bound iodine to Tg. Among these ratios, the sPBI/Tg ratio is particularly important as it signifies the amount of combined iodine per unit of Tg.
Currently, urinary iodine is the primary indicator for evaluating iodine nutritional status due to its ease of collection and the fact that over 90% of ingested iodine is excreted through urine [19]. However, urinary iodine levels can vary significantly on a daily basis and may not accurately reflect an individual's iodine nutritional status over an extended period of time [20]. Particularly in the context of AITD, there is a need for an indicator that can reflect recent iodine nutritional status. Serum iodine serves as an excellent alternative [21]. Dietary iodine is primarily absorbed in the small intestine and enters the bloodstream through the NIS transporter [22]. Serum iodine consists of two components: sPBI and snPBI.
In our study, the median urinary iodine level in the population was 146.46 µg/L, which fell within the iodine-sufficient range according to the WHO and ICCIDD standards [15]. Although there were variations in urinary iodine levels between urban (130.43 µg/L) and rural areas (160.74 µg/L), both remained within the suitable iodine range. The median serum iodine level was 72.59 µg/L, which fell within the normal reference interval as determined by Jin and Shen's studies [23, 24].
When analyzing the entire population, we observed that the positive rates of thyroid autoantibodies TPOAb and TgAb were significantly higher in the iodine-deficient group (< 100 µg/L) compared to the iodine-appropriate group. Furthermore, the positive rate of autoantibodies in the group with urinary iodine concentration below 50.74 µg/L was also higher than that in the 50.74-120.66 µg/L group. In terms of snPBI, using the 90% medical reference value to define the ranges, only the TPOAb positive rate exhibited differences between the < 21.86 µg/L and 21.86–52.87 µg/L groups. Similarly, in the sPBI analysis, the positive rates of TPOAb and TgAb in the < 19.65 µg/L group were significantly higher than those in the 19.65–77.92 µg/L group, using the 90% medical reference value as the defining range.
Furthermore, logistic regression analysis revealed that the risk of a positive TgAb rate was significantly higher in the group with UIC below 100 µg/L and the group with sPBI below 19.65 µg/L, compared to the higher iodine groups. In summary, we could preliminarily conclude that iodine deficiency led to an increase in TgAb concentration, which was consistent with previous research [25, 26]. The higher risk of positive thyroid autoantibodies observed in groups with lower snPBI and sPBI reference values suggested that the iodine bound by TG affected the TgAb titer. This finding might be attributed to the different immunogenicity of Tg at various degrees of iodination.
Our study focused on different forms of serum iodine, specifically sPBI and snPBI. We divided these forms into three categories based on the 90% medical reference value and examined their corresponding relationship with TgAb concentration. Our findings indicated that both males and females exhibited an increase in TgAb levels when serum iodine concentrations were either too low or too high, aligning with the conclusions drawn from urinary iodine analysis.
In women, lower levels of snPBI and sPBI, below the 90% medical reference value range, were associated with higher TgAb levels. Conversely, higher levels of snPBI and sPBI, above the 90% medical reference value range, were also linked to elevated TgAb levels. However, this phenomenon was less apparent in men, which might be attributed to the lower incidence of AITD in men compared to women [27]. The relationship between snPBI, sPBI, and TgAb might follow a nearly U-shaped curve, consistent with the findings of Zhang's study [28]. Notably, iodine in the serum is taken up by the thyroid gland, with a significant portion being absorbed by Tg. We hypothesized that the amount of iodine bound by Tg might impact its immunogenicity, consequently influencing the levels of TgAb.
We specifically focused on individuals who tested positive for autoantibodies, and we observed that the case group (autoantibody-positive group) exhibited higher levels of Tg and TgAb compared to the healthy control group. This finding further supported the strong association between AITDs and Tg and TgAb concentrations. In our case-control samples, we measured the Tg concentration in this subset of the population. Additionally, we calculated ratios of serum iodine, snPBI, and sPBI to Tg concentration. Of particular significance was the ratio of sPBI to Tg concentration, which represents the amount of iodine that can bind per unit of Tg. Previous studies have suggested that sPBI binds to tyrosine residues on Tg, leading to the iodination of Tg [29–31].
However, our investigation revealed that the ratio of snPBI to Tg concentration in the case group was significantly higher than that in the healthy control group. This finding suggested that as the degree of iodination of Tg increased, the immunogenicity of Tg might be enhanced, resulting in higher concentrations of TgAb. Consequently, TgAb attacked the thyroid gland, leading to the development of AITD.
Our research possessed several notable advantages. Firstly, based on the internal data from TIDE-2014, our study demonstrated a high level of reliability in data collection and sample processing. Furthermore, the previous research conducted by our project team has laid a solid foundation for the current investigation.
However, it is crucial to acknowledge the limitations of our study. The data we utilized only pertained to two districts in Tianjin. As Tianjin represents an iodine-appropriate area, it may not accurately reflect regions with low-water or high-water iodine levels. Moreover, while we employed a cross-sectional study design and conducted a comparison after, we are unable to establish a causal inference and can only speculate. Within the reference range we established, only values below the reference value exhibited significant statistical significance in relation to antibody positivity. Conversely, values above the reference value did not exhibit the same significance. This discrepancy might be attributed to the inadequate selection of an upper threshold. In our future research endeavors, we will actively explore an improved upper threshold. We intend to incorporate animal experiments and utilize cohort studies to verify our hypotheses and provide more comprehensive insights into the pathogenic mechanisms of AITD caused by iodine malnutrition.